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Izzy Livne-Bar, Jessica Wei, I-Ping Lee, Karsten Gronert, Jeremy M Sivak, John G Flanagan; Astrocyte-Produced Factors Protect Retinal Ganglion Cells from Acute Metabolic Stress. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4417.
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© ARVO (1962-2015); The Authors (2016-present)
Astrocytes and related Müller glia play critical homeostatic roles in the inner retina, and become activated upon retinal disease or injury. However, the impact of astrocyte activation on retinal ganglion cells (RGCs) remains unclear. We reported that quiescent retinal astrocytes promote RGCs survival following acute injury in vivo. Furthermore, we established that the protective activity is present in astrocyte-conditioned media. The purpose of this study was to characterize the lipid mediators (LM) in retinal astrocyte-conditioned media, and test specific LMs for their role in RGC protection.
Conditioned media from primary retinal astrocytes and control media were analyzed by LC-MS/MS to determine levels of LM production. The protective activity of the identified LMs was tested in HT22 neural cells exposed to glutamate insult. For in vivo validation, LMs were injected intravitreally prior to induction of acute insult with the glutamatergic analogue kainic acid (10 mM). RGC survival was quantified by immunofluorescence microscopy of treated and control eyes followed by image analyses and statistical evaluation.
We established that prostaglandins E2, D2 and F2a were enriched in astrocyte-conditioned media. However, astrocytes activated by oxidative stress, showed reduced production of these prostanoids. In addition, we found that an EP4 receptor agonist protected neural cells from glutamate toxicity in vitro. Our preliminary, in vivo, data indicated that this agonist promotes RGC survival following acute glutamatergic insult.
We demonstrated that resting retinal astrocytes produce LMs with neuroprotective activity and established that the EP4 receptor is involved in mediating this neuroprotection.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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